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TSE ADVISORY meeting October 31, 2005 [FR Doc. 05-20558] TSS

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----- Original Message -----
From: Terry S. Singeltary Sr.
To: [email protected]
Cc: [email protected] ; [email protected] ; [email protected]
Sent: Friday, October 14, 2005 12:11 PM
Subject: TSE ADVISORY meeting October 31, 2005 [FR Doc. 05-20558] TSS SUBMISSION


Greetings FDA TSE Advisory Committee Dr. Freas and Dr. Langford et al,


I wish to submit to the following [FR Doc. 05-20558],



[Federal Register: October 14, 2005 (Volume 70, Number 198)]
[Notices]
[Page 60095]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14oc05-53]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Transmissible Spongiform Encephalopathies Advisory Committee;
Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

This notice announces a forthcoming meeting of a public advisory
committee of the Food and Drug Administration (FDA). The meeting will
be open to the public.
Name of Committee: Transmissible Spongiform Encephalopathies
Advisory Committee.
General Function of the Committee: To provide advice and
recommendations to the agency on FDA's regulatory issues.
Date and Time: The meeting will be held on October 31, 2005, from 8
a.m. to 5:30 p.m.
Location: Holiday Inn Select, 8120 Wisconsin Ave., Bethesda, MD.
Contact Person: William Freas or Sheila D. Langford, Center for
Biologics Evaluation and Research (HFM-71), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314,
or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-
0572 in the Washington, DC area), code 3014512392. Please call the
Information Line for up-to-date information on this meeting.
Agenda: On October 31, 2005, the committee will hear updates on the
following topics: Current status of bovine spongiform encephalopathy
(BSE) in the United States, incidence and prevalence worldwide of
variant Creutzfeldt-Jakob Disease (vCJD), and a summary of FDA's device
panel discussion on September 27, 2005, on criteria for considering
label claims of effective decontamination for surgical instruments
exposed to transmissible spongiform encephalopathy (TSE) agents. The
committee will then discuss progress in development of a risk
assessment model for vCJD in U.S.-licensed human plasma-derived
Antihemophilic Factor (Factor VIII). The latter discussion will focus
on selection of input parameters for the model. In the afternoon, the
committee will discuss labeling claims for TSE clearance studies for
blood component filters.
Procedure: Interested persons may present data, information, or
views, orally or in writing, on issues pending before the committee.
Written submissions may be made to the contact person by October 21,
2005. Oral presentations from the public will be scheduled between
approximately 12:30 p.m. and 1 p.m., and 4:15 p.m. and 4:45 p.m. on
October 31, 2005. Time allotted for each presentation may be limited.
Those desiring to make formal oral presentations should notify the
contact person before October 25, 2005, and submit a brief statement of
the general nature of the evidence or arguments they wish to present,
the names and addresses of proposed participants, and an indication of
the approximate time requested to make their presentation.
Persons attending FDA's advisory committee meetings are advised
that the agency is not responsible for providing access to electrical
outlets.
FDA welcomes the attendance of the public at its advisory committee
meetings and will make every effort to accommodate persons with
physical disabilities or special needs. If you require special
accommodations due to a disability, please contact William Freas or
Sheila Langford at least 7 days in advance of the meeting.
Notice of this meeting is given under the Federal Advisory
Committee Act (5 U.S.C. app. 2).

Dated: October 6, 2005.
Jason Brodsky,
Acting Associate Commissioner for External Relations.
[FR Doc. 05-20558 Filed 10-13-05; 8:45 am]

BILLING CODE 4160-01-S


http://a257.g.akamaitech.net/7/257/2422/01jan20051800/edocket.access.gpo.gov/2005/05-20558.htm



Greetings again FDA et al,


NOTHING like ignoring the obvious, i.e. sporadic CJDs. sporadic CJDs are not one strain, but potentially multiple
strains with some being atypical. WITH the documentation of transmission of vCJD to humans by blood.
the recent study by Aguzzi et al Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion.
the recent study by Yoshifumi Iwamaru et al that Muscle tissue has recently been detected with PrPSc in the peripheral nerves
(sciatic nerve, tibial nerve, vagus nerve) of the 11th BSE cow in Japan.
and all the old studies from decades of research where sporadic CJD has transmitted via a multitude of routes and sources via the medical and surgical arena.
to continue to blatantly ignore the real ramifications of low level infectivity and accumulation with sporadic CJD and continue to only base risk assessment on
vCJD will only aid in the continued spreading and exposure of the sporadic CJDs in the medical and surgical arena. sCJD being just as deadly (100% fatal for those
that go clinical), just as hideous as the death of a nv/v CJD victim. I wish to reference the following studies in my previous submissions to Federal Dockets;



SEACEARLY PHASE OF vCJD INFECTION IN BLOOD TRANSFUSIONRECIPIENTS
http://www.seac.gov.uk/pdf/cjd.pdf



SEAC Statement7th August 2004 -------------------------------------------------------------------------------- Summary of SEAC’s discussion on the second presumed case of blood transfusion-associated infection with vCJD http://www.seac.gov.uk/statements/state070804.htm From: TSS ()Subject: Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion {FULL TEXT}Date: October 14, 2005 at 7:20 am PSTScience, Vol 310, Issue 5746, 324-326 , 14 October 2005 ReportsCoincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1 Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3 Gino Miele,1 Adriano Aguzzi1 Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread. 1 Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.2 Institute of Clinical Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.3 Institute of Biostatistics, University of Zürich, Sumatrastrasse 30, CH-8006 Zürich, Switzerland. * These authors contributed equally to this work. To whom correspondence should be addressed. E-mail: [email protected] snip...

www.sciencemag.org/





Materials and Methods

Figs. S1 to S5

Table S1

References

15 August 2005; accepted 18 September 2005
10.1126/science.1118829
Include this information when citing this paper.


http://www.sciencemag.org/


snip...end...TSS




Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION

http://docket.epa.gov/edkfed/do/EDKStaffItemDetailView?objectId=090007d480993808


http://docket.epa.gov/edkfed/do/EDKStaffAttachDownloadPDF?objectId=090007d480993808


http://docket.epa.gov/edkfed/do/EDKStaffCollectionDetailView?objectId=0b0007d48096b40d


[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirementsfor the Disposition of Non-Ambulatory Disabled Cattle http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf -------- Original Message -------- Subject: Blood Products Advisory Committee [FR Doc. 04-21283 Filed 9-21-04; 8:45 am] TSS SUBMISSIONDate: Wed, 22 Sep 2004 15:31:55 -0500From: "Terry S. Singeltary Sr." To: [email protected]: [email protected], [email protected], [email protected]
TSS SUBMISSION TO;Blood Products Advisory Committee[FR Doc. 04-21283 Filed 9-21-04; 8:45 am] Greetings Dr. Smallwood and all FDA, I kindly wish to submit the following information andcomments to the Blood Products Advisory Committee.I kindly wish to submit the following information andcomments to the TSE Advisory Committee on blood products. IF you remember correctly, in my submission of;Freas, William TSS SUBMISSIONFile Format: PDF/Adobe Acrobat -Page 1. J Freas, William From: Sent: To: Subject: Terry S. SingeltarySr. [[email protected]] Monday, January 08, 200l 3:03 PM freas ... snip... I am beginning to think that the endless attempt to trackdown and ban, potential victims from known BSE Countriesfrom giving blood will be futile. You would have to baneveryone on the Globe eventually? AS well, I think weMUST ACT SWIFTLY to find blood test for TSE's,whether it be blood test, urine test, eyelid test,anything at whatever cost, we need a test FAST. ,DO NOT let the incubation time period of theseTSEs fool you. snip... http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf NOW, some 3+ years later, seems we are faced with just thisnightmare scenario. Seems we have floundered too long, but myfear is that we are still missing the bigger picture, sporadic CJD.I have made several submissions to the FDA about my concernwith the transmission of the TSE agent from sporadic CJD viathe medical surgical arena and tissue transplantation; Docket ManagementDocket: 02N-0370 - Neurological Devices; Classification of Human Dura MaterComment Number: EC -1Accepted - Volume 1 http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be11.html http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfe.html http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfc.html I WISH to make the following submission and comments about alltopics of this meeting about human/animal TSEs. My comments andsubmissions as follows please; >USDA-licensed tests for the diagnosis of bovine>spongiform encephalopathy (BSE) and other transmissible spongiform>encephalopathies (TSE), >IN the past all we have heard is the fact that the present BSEs test do notguarantee public health safety. I request that the USA implement a BSE/TSE test that DOES guarantee public health safety, one approvedfor consumer protection, a test for live cattle, one that would detect allTSEs in the bovine, one that would detect sub clinical TSEs; EFSA Scientific Report on the Design of a Field Trial Protocol for theEvaluation of BSE Tests for Live CattlePublication date: 17 September 2004Adopted on 1 July 2004 (Question N° EFSA-Q-2003-084)* 146 kB Reporthttp://www.efsa.eu.int/science/efsa_scientific_reports/bse_tse/612/report09_bse02_tests_livecattle_en1.pdf * 90 kB Summaryhttp://www.efsa.eu.int/science/efsa_scientific_reports/bse_tse/612/bse02_sr09_tests_livecattle_summary_en1.pdf Summary of the ReportThe European Food Safety Authority and its Scientific Expert WorkingGroup on Transmissible Spongiform Encephalopathy (TSE) Testing wereasked by the European Commission (EC) to take over the mandate of theformer Scientific Steering Committee (SSC) for the scientific evaluationof rapid TSE/BSE (Bovine Spongiform Encephalopathy) tests. At present 5rapid BSE test kits are approved by the EC for the routine post mortemtesting of slaughtered cattle over 30 months of age in accordance withthe TSE Regulation (EC) No 999/2001. Following a call for expression ofinterest in the Official Journal of the European Union (No C15) on 22January 2003, several parties indicated their interest in participatingin an EC evaluation exercise of their newly developed rapid BSE postmortem and live animal tests.It has been recognized that the availability of a rapid test for livecattle would be a major advance in dealing with the problem of BSE andTSE in general, but particularly with regard to epidemiologicalscreening. In the long term an accurate live animal test might offer thepossibility to reduce the number of culled animals after the detectionof one positive animal.A rapid BSE test for live cattle could be approved for the purpose ofconsumer protection, for epidemiological screening or for both. For thepurpose of consumer protection any new rapid BSE test including testsfor live animals should not be statistically inferior to that of thecurrently approved post mortem tests.This report provides a protocol for the design of a field trial protocolfor the evaluation of BSE tests for live cattle for the purpose ofconsumer protection only. http://www.efsa.eu.int/science/efsa_scientific_reports/bse_tse/612_en.html FULL TEXT; http://www.efsa.eu.int/science/efsa_scientific_reports/bse_tse/612/report09_bse02_tests_livecattle_en1.pdf >review of the worldwide BSE situation, > THE most disturbing factor of this topic are the new atypical TSEsshowing up in not only cattle, but also sheep, and no one know's yetabout how many different strains of cwdTSE in deer/elk. WITH evidence ofsporadic CJD being very similar to these atypical TSEs in cattle and sheep,and the findings from Asante, Collinge et al that BSE prions propagateas either nvCJD or sporadic CJD, the ramifications of these findings are very very worrysome and should not go ignored any further. WITHthe fact that there are over 20 documented strains of scrapie, and themost logical hypothisis is scrapie to BSE, why would one believe inonly one phenotype of TSE in the bovine; BSE prions propagate as either variant CJD-like or sporadic CJD-likeprion strains in transgenic mice expressing human prion protein Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth and John Collinge1MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1 Corresponding author e-mail: [email protected] Received August 1, 2002; revised September 24, 2002; accepted October 17, 2002 Abstract Variant CreutzfeldtJakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure...http://embojournal.npgjournals.com/cgi/content/full/21/23/6358THE new findings of BASE in cattle in Italy of Identification of asecond bovine amyloidotic spongiform encephalopathy: Molecularsimilarities with sporadic Creutzfeldt-Jakob disease http://www.pnas.org/cgi/content/abstract/0305777101v1 Characterization of two distinct prion strainsderived from bovine spongiform encephalopathytransmissions to inbred mice Sarah E. Lloyd, Jacqueline M. Linehan, Melanie Desbruslais,Susan Joiner, Jennifer Buckell, Sebastian Brandner,Jonathan D. F. Wadsworth and John CollingeCorrespondenceJohn [email protected] Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology,University College, London WC1N 3BG, UKReceived 9 December 2003Accepted 27 April 2004Distinct prion strains can be distinguished by differences in incubation period, neuropathologyand biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice.Reliable comparisons of mouse prion strain properties can only be achieved after passage ingenetically identical mice, as host prion protein sequence and genetic background are knownto modulate prion disease phenotypes. While multiple prion strains have been identified insheep scrapie and CreutzfeldtJakob disease, bovine spongiform encephalopathy (BSE) isthought to be caused by a single prion strain. Primary passage of BSE prions to different linesof inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that twoprion strains may have been isolated. To investigate this further, these isolates weresubpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prionstrains had been identified. MRC1 was characterized by a short incubation time (110±3 days),a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactivedeposits, while MRC2 displayed a much longer incubation time (155±1 days),a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP-immunoreactive depositsand neuronal loss. These data indicate a crucial involvement of the host genome in modulatingprion strain selection and propagation in mice. It is possible that multiple disease phenotypesmay also be possible in BSE prion infection in humans and other animals.http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471Adaptation of the bovine spongiform encephalopathy agent to primatesand comparison with Creutzfeldt- Jakob disease: Implications forhuman healthTHE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*,Virginie Nouvel*,Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , DominiqueDormont*, and Jean-Philippe Deslys* et al, that The agent responsiblefor French iatrogenic growth hormone-linked CJD taken as a control isvery different from vCJD but is similar to that found in one case ofsporadic CJD and one sheep scrapie isolate; http://www.pnas.org/cgi/content/full/041490898v1 THE recent discoveries of previously unidentified strains ofScrapie such as 221C44 and the Nor9845;2.5.2 The existence of distinct strains was recognised when sources ofsheep scrapie were serially transmitted to mice. A single inbred line of mice, in which allindividuals make the same PrPC, can propagate several different strains of scrapie, each withits own distinctive incubation period, pattern of damage in the brain and PrPScproperties42, 43. Strain variation also occurs in natural scrapie, and the recent discoveries ofpreviously unidentified strains, such as 221C44 and Nor9845, suggests that thespectrum of different strains may change with time. Since different strains can have verydifferent patterns of pathology and distribution of PrPSc, their presence may be missed by theapplication of standard sampling and testing protocols used for surveillance45.Although a single strain of BSE appears to be responsible for the vast majority of cases around theworld46, 47, evidence is emerging that suggests that there may be other strains whichhave different properties when transmitted to mice48 or result in different pathologyor properties of PrPSc in infected cattle49, 50.FULL TEXT APPRX. 91 PAGESUK Strategy for Research andDevelopment on Human and AnimalHealth Aspects of TransmissibleSpongiform Encephalopathies2004-2007 http://www.mrc.ac.uk/pdf-uk_strategy_v5.2.pdf WHEN in fact, the findings from Marsh and the findings atMISSION, TEXAS support even further evidence that thereare furthers strains of TSE in the USA besides that oneaccidently documented BSE case in Washington onDec. 23, 2003;In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - Report of a visit to the USA - April-May 1989 - G A H Wells [head of England's main veterinary lab]2. Meeting with USDA, BSE Task ForceThis group comprises Alex Thierman (USDA-APHIS, International Programs)(Chairman), Roger Breeze (USDA-ARS Director, Plum Island), Bill Hadlow(Neuropathologist - retired, formerly of NIH Rocky Mountain Laboratory, Hamilton, Montana), John Gorhan and Mark Robinson (USDA-ARS, Pullman, Washington) and Dick Marsh (Dept. Vet. Science, Univ Wisconsin - Madison). The objectives of the group are to assess the implications of the occurrence of BSE for US cattle particularly the risk of BSE occurrence in the US in relation to endemic scrapie agent.The purpose of my invitation to this meeting was to discuss aspects ofresearch which are of common interest and to identify a tentative USDAresearch programme including any potential collaborative projects. Thediscussions were informal and there was no agenda. The general opinionof those present was that BSE, as an overt disease phenomenon, couldexist in the USA but if it did it was very rare. The need for improvedand specific surveillance methods to detect it was recognised. Clinicalsimilarities between BSE and rabies suggested one means of sampling thecattle population which might increase the probability of detection ofBSE. It was clear that the bovine rabies negative rate would varygreatly between States but initially this should be determined and as itwould inevitably be high relative to positive cases, some differentialdiagnosis carried out.The work of Wilbur Clarke at Mission, Texas was discussed briefly. theresults of this study in which 10 calves were inoculated with scrapiehas not been published and perhaps would not be published. USDA aresensitive regarding publicity of the results of the study which remainfar from conclusive. Apparently only 3 of the inoculated animalsdeveloped neurological signs. The neuropathology of the affected cattlehas not been examined in any depth but Hadlow has the material. Marshindicated the requirement to obtain the fresh brain material from thisstudy in order to perform PrP extractions.Because of the successful transmission of the Brecke (Stetsonville)isolate of TME to cattle and the subsequent passage history in mink itwas generally considered important that comparisons be made with BSEisolates in mink. Is BSE like scrapie in mink? Is BSE like the Breckeisolate of TME?Very little was said about CWD but some present considered that itsoccurrence may indicate a sylvatic origin of agent. It was also agreedthat the role of possible subclinical infection in theepidemiology of transmissible spongiform encephalopathies could wellbe important but was unknown. Marsh remarked on the possibility thatBSE was due to an extremely thermostable strain of agent. Hisexperience in the past with one particular Wisconsin isolate of TME(Hayward strain) suggested that i/c biopsy needles could not beeffectively "scrapie sterilised", even employing an experimentalautoclave system capable of 60 psi and 300"C+ for 5 hours. Thisexperience led him to the policy that in scrapie or TME transmissionstudies re-use of instruments or glassware that had contained agent wasan unacceptable protocol.I was given confidential access to sections from the Clarke scrapie- cattle transmission experiment. Details of the experimental design were as supplied previously by Dr Wrathall (copy of relevant informationappended). Only 3 animals (2 inoculated with 2nd pass Suffolk Scrapieand 1 inoculated with Angora goat passaged scrapie) show clinical signs.Clinical signs were characterised by weakness, "a stilted hindlimb gait", disorientation, ataxia and, terminally,lateral recumbency. The two cattle from which I examined material wereinoculated at 8 months of age and developed signs 36 months pi (goatscrapie inoculum) and 49 months pi (one of the Suffolk scrapieinoculated) respectively. This latter animal was killed at 58 monthsof age and so the clinical duration was only 1 month. The neuropathologywas somewhat different from BSE or the Stetsonville TME in cattle.Vacuolar changes were minimal, to the extent that detection requiredcareful searching. Conversely astrocyte hypertrophy was a widespread andprominent feature. The material requires detailed neuropathologicalassessment but whether or not this will be done remains in question.Appendix IVISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE1. Dr Clark lately of the Scrapie Research Unit, Mission Texas hassuccessfully transmitted ovine and caprine scrapie to cattle. Theexperimental results have not been published but there are plans to dothis. This work was initiated in 1978. A summary of it is:-Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a2nd Suffolk scrapie passage:-i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.1/6 went down after 48 months with a scrapie/BSE-like disease.Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus2/6 went down similarly after 36 months.Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.Diagnosis in A, B, C was by histopath. No reports on SAF were given.Dr Warren Foote indicated success so far in eliminating scrapie inoffspring from experimentally (and naturally) infected sheep by ET. Hehad found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).3. Prof. A Robertson gave a brief account of BSE. The US approach was toaccord it a very low profile indeed. Dr A Thiermann showed the picturein the "Independent" with cattle being incinerated and thought this wasa fanatical incident to be avoided in the US at all costs. BSE was notreported in USA.4. Scrapie incidents (ie affected flocks) have shown a dramatic increasesince 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.5. Scrapie agent was reported to have been isolated from a solitary fetus.6. A western blotting diagnostic technique (? on PrP) shows some promise.7. Results of a questionnaire sent to 33 states on the subject ofthe national sheep scrapie programme survey indicated;17/33 wished to drop it6/33 wished to develop it8/33 had few sheep and were neutralInformation obtained from Dr Wrathall's notes of a meeting of the U.S.Animal Health Association at Little Rock, Arkansas Nov. 1988.CONFIDENTIAL TRANSMISSION (Day 4)6.1 BSE to pigssnip...end full text ; http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf To be published in the Proceedings of theFourth International Scientific Congress inFur Animal Production. Toronto, Canada,August 21-28, 1988Evidence That Transmissible Mink EncephalopathyResults from Feeding Infected CattleR.F. Marsh* and G.R. Hartsough"Department of Veterinary Science, University of Wisconsin-Madison, Madison,Wisconsin 53706; and ^Emba/Creat Lakes Ranch Service, Thiensville, Wisconsin 53092ABSTRACTEpidemiologic investigation of a new incidence oftransmissible mink encephalopathy (TME) in Stetsonville, Wisconsinsuggests that the disease may have resulted from feeding infectedcattle to mink. This observation is supported by the transmission ofa TME-like disease to experimentally inoculated cattle, and by therecent report of a new bovine spongiform encephalopathy inEngland.INTRODUCTIONsnip...Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died fromTME.Since previous incidences of TME were associated with common or shared feedingpractices, we obtained a careful history of feed ingredients used over the past 12-18months. The rancher was a "dead stock" feeder using mostly (>95%) downer or dead dairycattle and a few horses. Sheep had never been fed.Experimental Transmission. The clinical diagnosis of TME was confirmed byhistopaihologic examination and by experimental transmission to mink after incubationperiods of four months. To investigate the possible involvement of cattle in this diseasecycle, two six-week old castrated Holstein bull calves were inoculated intracerebrallywith a brain suspension from affected mink. Each developed a fatal spongiformencephalopathy after incubation periods of 18 and 19 months.DISCUSSIONThese findings suggest that TME may result from feeding mink infected cattle andwe have alerted bovine practitioners that there may exist an as yet unrecognizedscrapie-like disease of cattle in the United States (Marsh and Hartsough, 1986).snip... full text; http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf Recently the question has again been brought up as to whetherscrapie is transmissible to man. This has followed reports that thedisease has been transmitted to primates. One particularly luridspeculation (Gajdusek 1977) conjectures that the agents of scrapie,kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy ofmink are varieties of a single "virus". The U.S. Department ofAgriculture concluded that it could "no longer justify or permitscrapie-blood line and scrapie-exposed sheep and goats to be processedfor human or animal food at slaughter or rendering plants" (ARC 84/77)"The problem is emphasised by the finding that some strains of scrapieproduce lesions identical to the once which characterise the humandementias"Whether true or not. the hypothesis that these agents might betransmissible to man raises two considerations. First, the safetyof laboratory personnel requires prompt attention. Second, actionsuch as the "scorched meat" policy of USDA makes the solution of theacrapie problem urgent if the sheep industry is not to suffergrievously.snip... 76/10.12/4.6 http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf http://www.bseinquiry.gov.uk/files/yb/1976/10/12002001.pdf BSE TO PIG The neuropathology of experimental bovine spongiform encephalopathyin the pig.Ryder SJ, Hawkins SA, Dawson M, Wells GA.Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw,Addlestone, Surrey, KT15 3NB, UK.In an experimental study of the transmissibility of BSE to the pig,seven of 10 pigs, infected at 1-2 weeks of age by multiple-routeparenteral inoculation with a homogenate of bovine brain fromnatural BSE cases developed lesions typical of spongiformencephalopathy. The lesions consisted principally of severe neuropilvacuolation affecting most areas of the brain, but mainly theforebrain. In addition, some vacuolar change was identified in therostral colliculi and hypothalamic areas of normal control pigs. PrPaccumulations were detected immunocytochemically in the brains ofBSE-infected animals. PrP accumulation was sparse in many areas andits density was not obviously related to the degree of vacuolation.The patterns of PrP immunolabelling in control pigs differedstrikingly from those in the infected animals.PMID: 10684682 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract >new FDA/Center for Food Safety and Applied Nutrition BSE-food safety rules, >FDA again is missing the bigger picture, ALL TSEs! THE BSE/nvCJD only theory should be trashedonce and for all. the name should read;new FDA/Center for Food Safety and Applied Nutrition TSE-food safety rules>and>labeling claims for TSE clearance studies for plasma derivative>products. >>The committee will then discuss and make recommendations>regarding presumptive transfusion transmissions of variant Creutzfeldt>Jakob Disease (vCJD) and current FDA-recommended safeguards.>ONE of the things i have been most worried about and will continue to bring to the attention of theTSE advisory committee is the continued denial of the potential of transmission of sporadic CJDvia blood and blood products. THERE are studies showing infectivity in the blood of sporadic CJD,and just how many phenotypes there are of sporadic CJD is anyone's guess at this point in time.WE have already documented transmission of sporadic CJD via tissues and organs.TO continue the BSE/nvCJD only theory will only continue to spread this agent. WE must moveaway from this mentality and move on with all TSEs and treat all TSEs as one, until proven otherwise,not the other way around. with 6,000 'DEAR nvCJD LETTERS' due to blood and blood products so far,i can only imagine the number, once sporadic CJD is documented to have transmitted via blood, what thatnumber will be when those 'DEAR SPORADIC CJD LETTERS' go out and how many will becomeclinical once exposed, a frightening thought;It is possible to transmit BSE to a sheepby transfusion with whole blood taken fromanother sheep during the symptom-free phaseof an experimental BSE infection'It is well known that variant Creutzfeldt-Jakobdisease (vCJD) is caused by the same strain ofagent that causes bovine spongiform encephalopathy(BSE) in cattle. F Houston and colleaguesreport the preliminary findings of transfusingblood from 19 UK Cheviot sheep fed with 5 gBSE-affected cattle brain into Cheviot sheep fromscrapie-free flock of New Zealand-derivedanimals. The investigators found BSE clinicalsigns and pathology in one recipient of blood takenfrom a BSE infected animal. Immunocytochemistry ontissues taken from the transfused sheepshowed widespread PrPSC deposition throughout thebrain and the periphery. This findingsuggests that blood donated by symptom-freevCJD-infected human beings could transmitinfection to recipients of blood transfusions.In a Commentary, Paul Brown states that theseobservations are consistent with previous reportsin experimentally infected rodents.==================Research lettersVolume 356, Number 9234 16 September 2000Transmission of BSE by blood transfusion in sheepLancet 2000; 356: 999 - 1000Download PDF (1 Mb)F Houston, J D Foster, Angela Chong, N Hunter, C J BostockSee CommentaryWe have shown that it is possible to transmitbovine spongiform encephalopathy (BSE)to a sheep by transfusion with whole bloodtaken from another sheep during thesymptom-free phase of an experimental BSEinfection. BSE and variantCreutzfeldt-Jakob disease (vCJD) in humanbeings are caused by the same infectiousagent, and the sheep-BSE experimental modelhas a similar pathogenesis to that ofhuman vCJD. Although UK blood transfusionsare leucodepleted--a possible protectivemeasure against any risk from bloodtransmission--this report suggests that blooddonated by symptom-free vCJD-infected humanbeings may represent a risk of spreadof vCJD infection among the human populationof the UK.The demonstration that the new variant ofCreutzfeldt-Jakob disease (vCJD) is caused by thesame agent that causes bovine spongiformencephalopathy (BSE) in cattle1 has raised concernsthat blood from human beings in the symptom-freestages of vCJD could transmit infection torecipients of blood transfusions. There is noevidence that iatrogenic CJD has ever occurred as aresult of the use of blood or blood products,but vCJD has a different pathogenesis and couldpresent different risks. CJD is one of thetransmissible spongiform encephalopathies (TSEs)characterised by the deposition of an abnormalform of a host protein, PrPSc; the normalisoform (PrPC) is expressed in many body tissues.Available evidence, based on detection ofinfectivity in blood in rodent models, and absenceof infectivity in naturally occurring TSEs, addsto the uncertainty in risk assessments of thesafety of human blood. PrPSc has been reported inblood taken from preclinical TSE-infected sheep,2but it does not follow that blood is infectious.Bioassays of human blood can only be carried outin non-human species, limiting the sensitivityof the test. One way of avoiding such a speciesbarrier is to transfer blood by transfusion in anappropriate animal TSE model. BSE-infected sheepharbour infection in peripheral tissues3 andare thus similar to humans infected with vCJD.4BSE infectivity in cattle does not havewidespread tissue distribution.We report preliminary data from a studyinvolving blood taken from UK Cheviot sheepchallenged orally with 5 g BSE-affected cattlebrain and transfused into Cheviot sheep from ascrapie-free flock of New Zealand-derived animals(MAFF/SF flock). MAFF/SF sheep do notdevelop spontaneous TSE and the transfusedanimals are housed separately from other sheep.All sheep in the study have the PrP genotypeAA136QQ171 which has the shortest incubationperiod of experimental BSE in sheep.5 19 transfusions fromBSE-challenged sheep have beendone, mostly with whole blood. Sheep havecomplex blood groups and only simplecross-matching can be done by mixing recipientserum and donor erythrocytes and vice versa.Therefore single transfusions only were madebetween sedated cross-matched animals tominimise the risk of severe reactions. Negativecontrols were MAFF/SF sheep transfused withblood from uninfected UK Cheviot sheep. As apositive control, MAFF/SF sheep wereintravenously injected with homogenised BSE-affectedcattle brain.We have seen BSE clinical signs and pathologicalchanges in one recipient of blood from aBSE-infected animal, and we regard this findingas sufficiently important to report now ratherthan after the study is completed, several yearshence. The blood donation resulting intransmission of BSE to the recipient was 400 mLof whole blood taken from a healthy sheep318 days after oral challenge with BSE. BSE subsequentlydeveloped in this donor animal 629days after challenge, indicating that blood was takenroughly half way through the incubationperiod. 610 days after transfusion, the transfusedsheep (D505) itself developed typical TSEsigns: weight loss, moderate pruritus, tremblingand licking of the lips, hind-limb ataxia, andproprioceptive abnormalities. This is the firstexperimental transmission of BSE from sheep tosheep and so we have nothing with which to comparethis incubation period directly. Incross-species transmissions, bovine BSE injectedintracerebrally gives incubation periods ofabout 450 days in these sheep,5 and the donor animalhad an oral BSE incubation period of 629days (see above). There are no similar dataavailable on other infection routes.Immunocytochemistry with the antibody BG4 on tissuestaken from sheep D505 showedwidespread PrPSc deposition throughout the brain andperiphery. Western blot analysis of braintissue with the antibody 6H4 showed that the PrPScprotein had a glycoform pattern similar tothat of experimental BSE in sheep and unlike thatof UK natural scrapie (figure), indicating thatthe TSE signs resulted from transmissionof the BSE agent. All other recipients of transfusionsand positive and negative controls arealive and healthy. The positive controls, which involve aspecies barrier, are expected to havelengthy incubation periods. With one exception, alltransfused animals are at earlier stagespost-transfusion than was D505. The exception is asheep which is healthy 635 days after transfusionwith BSE-blood donated at less than 30% ofthe BSE incubation period of the donor sheep.PrPSc (proteinase K treated) analysed by SDS-PAGE,immunoblotted with 6H4, andvisualised with a chemiluminescent substrateAll lanes are from the same gel with differentexposure times. Size markers are to the left oflane 1. Lane1: natural scrapie sheep brain,3 min exposure. Lane 2: as lane 1, 10 min exposure.Lane 3: sheep D505, blood-transfusionrecipient, 10 min exposure. Lane 4: experimentalBSE-affected sheep brain, 30 s exposure.Lane 5: as lane 4, 10 min exposure. Each laneloaded with amount of protein extracted from0·1 g wet weight of brain, except lane 3 whichwas extracted from 0·2 g brain.Although this result was in only one animal, itindicates that BSE can be transmitted betweenindividuals of the same species by whole-bloodtransfusion. We have no data on blood fractionsor on levels of infectivity in blood of preclinicalvCJD cases, but whole blood is not now used inUK transfusions. The presence of BSE infectivityin sheep blood at an early stage in theincubation period suggests that it should bepossible to identify which cells are infected, to testthe effectiveness of leucodepletion, and todevelop a diagnostic test based on a blood sample.We thank Karen Brown, Moira Bruce, CalumMcKenzie, David Parnham, Diane Ritchie, andthe Scottish Blood Transfusion Service. Theproject is funded by the Department of Health.1 Bruce ME, Will RG, Ironside JW, et al.Transmissions to mice indicate that 'new variant' CJDis caused by the BSE agent. Nature 1997;389: 488-501 [PubMed].2 Schmerr MJ, Jenny A, Cutlip RC. Use ofcapillary sodium dodecyl sulfate gel electrophoresisto detect the prion protein extracted fromscrapie-infected sheep. J Chromatogr B BiomedAppl 1997; 697: 223-29 [PubMed].3 Foster JD, Bruce M, McConnell I, Chree A,Fraser H. Detection of BSE infectivity in brainand spleen of experimentally infected sheep.Vet Rec 1996; 138: 546-48 [PubMed].4 Hill AF, Zeidler M, Ironside J, Collinge J.Diagnosis of new variant Creutzfeldt-Jakob diseaseby tonsil biopsy. Lancet 1997; 349: 99-100.5 Goldmann W, Hunter N, Smith G, Foster J,Hope J. PrP genotype and agent effects inscrapie: change in allelic interaction withdifferent isolates of agent in sheep, a natural host ofscrapie. J Gen Virol 1994; 75: 989-95 [PubMed].Institute for Animal Health, Compton, Newbury,UK (F Houston PhD, CJ BostockPhD); and Institute for Animal Health, Neuropathogenesis Unit,Edinburgh, EH93JF, UK (N Hunter PhD, JD Foster BSc, Angela Chong BSc)Correspondence to: Dr N HunterALSO;Transmission of prion diseases by blood transfusionNora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 DavidParnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2see full text; http://www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf =======================CommentaryVolume 356, Number 9234 16 September 2000BSE and transmission through bloodLancet 2000; 356: 955 - 956Download PDF (55 Kb)snip...Blood from four of 37 human beings withclinically evident sporadic CJD has been reportedto transmit the disease after intracerebral inoculation into guineapigs,mice, or hamsters. But eachsuccess has been questioned on technical groundsand has not been reproducible;snip...Is it appropriate to publish an experimentalresult from a single animal in a study that is not farenough along even to have validated its positivecontrols? Especially a result that does not in anyfundamental way change our current thinking aboutBSE and vCJD and which would not seemto have any practical consequences for publichealth? The UK National Blood TransfusionService has already implemented leucodepletionof donated blood, and imports all plasma andplasma derivatives from BSE-free countries. Nofurther measures would seem possible--shortof a draconian decision to shut down the wholeUK blood-donor system. What, therefore, is therationale for this publishing urgency? Theanswer, evidently, is a perceived need to "defuse", byan immediate and accurate scientific report,public reaction to possibly inaccurate mediaaccounts. The full study, when it appears, willbe an important addition to our knowledge ofTSEs, but science should not be driven to whatin certain medical quarters might be termed apremature emission through fear of media misrepresentation.Paul BrownLaboratory of Central Nervous System Studies,National Institutes of Health, Bethesda,MD 20892, USAhttp://www.thelancet.com/> What, therefore, is the> rationale for this publishing urgency? Wonder what Dr. Paul Brown would think of this stupid statement now?SEEMS the urgency was and is a long time coming. HOW many moredo we expose with 'rationale' such as Paul Browns?Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into MiceThe Lancet, November 9, 1985Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) reporttransmission to animals of Creutzfeldt-Jakob disease (CJD) from thebuffy coat from two patients. We also transmitted the disease fromwhole blood samples of a patient (and of mice) infected with CJD.1Brain, Cornea, and urine from this patient were also infectious, andthe clinicopathological findings2 are summarised as follows.A 70-year-old man was noted to have a slowing of speech and writingand some disorientation, all of which progressed rapidly. Decorticaterigidity, forced grasping, positive snout reflex, and myoclonusappeared within 2 months. Electroencephalogram revealed typicalperiodic synchronous discharge, and he died of pneumonia and uppergastrointestinal haemorrhage, about 3 months after onset of thesymptoms. The Brain weighed 1290g and showed severe histologicalchanges diagnostic of CJD, including spongiform change, loss ofnerve cells, and diffuse proliferation of astrocytes. There were noinflammatory cells, microglia, neurofibrillary tangles, andamyloid plaques, although virus-like particles were detected byelectron microscopy.Results of innoculation in MiceInocula NO* Incubation period (days)+Brain 7/10 (4) 789 (+ or - 112)Cornea 1/6 (0) 1037Blood 2/13 (0) 1080 (+ or - 69)Urine 5/10 (1) 880 (+ or - 55)CSF 0/10* Number of mice with CJD change/number examined histologically.Number with amyloid plaques shown in parentheses.+ means + or - SDSamples were taken aseptically at necropsy. 10% crude homogenatesof brain and cornea in saline, whole blood (after crushing a clot),and untreated CSF and urine were innoculated intracerebrally intoCF1 strain mice (20 ul per animal). Some mice showed emaciation,bradykinesia, rigidity of the body and tail, and sometimes tremorafter long incubation periods. Tissues obtained after the animaldied (or was killed) were studied histologically (table). Animalsinfected by various inocula showed common pathological changes,consisting of severe spongiform changes, glial proliferation, anda moderate loss of nerve cells. A few mice inoculated with braintissue or urine had the same amyloid plaques found in patients andanimals with CJD.3In our long-term experiments, inoculating materials taken fromtwenty patients with CJD or Gerstmann-Straussler-Scheinker'sdisease (GSS) into rodents, positive results were obtained inseventeen cases, including this patient. Brain tissue transmittedthe disease most frequently within the shortes incubation period,except for one case where the lymph node was the most infectious.Transmission through the cornea has been noted in man4 and inguineapigs.5 Whole blood samples taken from three patients wereinoculated and a positive transmission occured only in the caserecorded here. Mouse-to-mouse transmission through bloodinoculation was successful after a mean incubation period of 365days.1 Transmission through urine was positive in this patientonly, and negative in one other patient and in many infected animals.Transmission through the CSF from eight patients was negative, yettransmission via the CSF of infected rats was positive.1As viraemia has been proved in guineapigs,6 mice,1,7 and latelyin patients with CJD, blood for transfusion or blood products formedical use must be tested for unconventional pathogens. For thispurpose, we inoculated blood products inot rodents.8 The CJDpathogen was not found in the products examined. However, thisapproach takes too long to be of practical value. More efficientmethods must be developed to detect pathogens and to eliminatethem from blood. One proposal9 is to apply membrane filtration tothe pruification protocol of human growth hormone suspected ofbeing contaminated with CJD. Similar methods are needed for bloodcontamination.Department of Neuropathology,Neurological Institute,Faculty of Medicine,Kyushu University,Fukuoka812, JapanJUN TATEISHI1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmissionof human subacute spongiform encephalopathy to smallrodents 1: Clinical and histological observations.Acta Neuropathol (Berl) 1980; 51: 127.2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakobdisease with demonstration of virus-like particles.Acta pathol Jpn 1982;32: 695.3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in thebrains of mice with Creutzfeldt-Jakob disease.Ann Neurol 1984; 15: 278.4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D.Possible person-to-person transmission of Creutzfeldt-Jakob disease.N Engl J Med 1974; 290: 692.5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L.Experimental Creutzfeldt-Jakob disease transmitted via the eyewith infected cornea. N Engl J Med 1977; 296: 1334.6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimentalCreutzfeldt-Jakob disease. Science 1978: 200: 1069.7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC.Creutzfeldt-Jakob disease in mice. Persistent viremiam andpreferential replication of virus in low-density lymphocytes.Infect Immun 1983; 41: 154.8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiformencephalopathis absent in blood products. J Med Virol 1985; 15: 11.9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob diseasepathogen in growth hormone preparations is eliminatable.Lancet (in press).============ TransfusionVolume 42 Issue 5 Page 513 - May 2002doi:10.1046/j.1537-2995.2002.00098.x Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinus Nöelle Bons, Sylvain Lehmann, Nadine Mestre-Francès, Dominique Dormont, and Paul BrownBACKGROUND: More than 100 cases of variant CJD resulting from infections with bovine spongiform encephalopathy (BSE) have accumulated in the United Kingdom since 1995. Concern about the possibility of secondary transmissions via blood and blood components donated by infected individuals has prompted a variety of international donor deferral policies that will continue until laboratory and epidemiologic evidence provides a consensus about potential risk. STUDY DESIGN AND METHODS: BSE was passaged through macaque monkeys andthen adapted to the prosimian microcebe (Microcebus murinus ). Brainhomogenate and buffy coat from an affected microcebe were separatelyinoculated intracerebrally into three healthy microcebes (two animalsreceived brain and one received buffy coat).RESULTS: All three inoculated microcebes became ill after incubationperiods of 16 to 18 months. Clinical, histopathologic, andimmunocytologic features were similar in each of the recipients.CONCLUSION: Buffy coat from a symptomatic microcebe infected 17 monthsearlier with BSE contained the infectious agent. This observationrepresents the first documented transmission of BSE from the blood of anexperimentally infected primate, which in view of rodent buffy coatinfectivity precedents and the known host range of BSE is neitherunexpected nor cause for alarm. http://www.blackwell-synergy.com/servlet/useragent?func=synergy&synergyAction=showAbstract&doi=10.1046/j.1537-2995.2002.00098.x Prions in skeletal musclePatrick J. Bosque*,dagger ,Dagger , Chongsuk Ryou*, Glenn Telling*,§,David Peretz*,dagger , Giuseppe Legname*,dagger , Stephen J.DeArmond*,dagger ,¶, and Stanley B. Prusiner*,dagger ,||,*** Institute for Neurodegenerative Diseases and Departments of daggerNeurology, ¶ Pathology, and || Biochemistry and Biophysics, Universityof California, San Francisco, CA 94143Contributed by Stanley B. Prusiner, December 28, 2001Considerable evidence argues that consumption of beef products fromcattle infected with bovine spongiform encephalopathy (BSE) prionscauses new variant Creutzfeldt-Jakob disease. In an effort to preventnew variant Creutzfeldt-Jakob disease, certain "specified offals,"including neural and lymphatic tissues, thought to contain high titersof prions have been excluded from foods destined for human consumption[Phillips, N. A., Bridgeman, J. & Ferguson-Smith, M. (2000) in The BSEInquiry (Stationery Office, London), Vol. 6, pp. 413-451]. Here wereport that mouse skeletal muscle can propagate prions and accumulatesubstantial titers of these pathogens. We found both high prion titersand the disease-causing isoform of the prion protein (PrPSc) in theskeletal muscle of wild-type mice inoculated with either the Me7 orRocky Mountain Laboratory strain of murine prions. Particular musclesaccumulated distinct levels of PrPSc, with the highest levels observedin muscle from the hind limb. To determine whether prions are producedor merely accumulate intramuscularly, we established transgenic miceexpressing either mouse or Syrian hamster PrP exclusively in muscle.Inoculating these mice intramuscularly with prions resulted in theformation of high titers of nascent prions in muscle. In contrast,inoculating mice in which PrP expression was targeted to hepatocytesresulted in low prion titers. Our data demonstrate that factors inaddition to the amount of PrP expressed determine the tropism of prionsfor certain tissues. That some muscles are intrinsically capable ofaccumulating substantial titers of prions is of particular concern.Because significant dietary exposure to prions might occur through theconsumption of meat, even if it is largely free of neural and lymphatictissue, a comprehensive effort to map the distribution of prions in themuscle of infected livestock is needed. Furthermore, muscle may providea readily biopsied tissue from which to diagnose prion disease inasymptomatic animals and even humans. Dagger Present address: Departmentof Medicine, Denver Health Medical Center, Denver, CO 80204.§ Present address: Department of Microbiology and Immunology, Universityof Kentucky, Lexington, KY 40536-0230.** To whom reprint requests should be addressed. E-mail: [email protected]/cgi/doi/10.1073/pnas.052707499 http://www.pnas.org/cgi/content/abstract/99/6/3812?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=prusiner&author2=prusiner&titleabstract=prions+meat+tissue+mice&fulltext=prions+meat+tissue+mice&searchid=1024346978866_6016&stored_search=&FIRSTINDEX=0&fdate=1/1/2002 FULL TEXT; http://www.pnas.org/cgi/content/full/99/6/3812?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=prusiner&author2=prusiner&titleabstract=prions+meat+tissue+mice&fulltext=prions+meat+tissue+mice&searchid=1050249844061_1953&stored_search=&FIRSTINDEX=0&fdate=1/1/2002
Extraneural Pathologic Prion Protein in Sporadic Creutzfeldt-Jakob DiseaseMarkus Glatzel, M.D., Eugenio Abela, Manuela Maissen, M.S., and Adriano Aguzzi, M.D., Ph.D.snip...Conclusions Using sensitive techniques, we identified extraneural depositionof PrPSc in spleen and muscle samples from approximately one third of patientswho died with sporadic Creutzfeldt-Jakob disease. Extraneural PrPSc appearsto correlate with a long duration of disease.http://content.nejm.org/cgi/content/short/349/19/1812?query=TOCEMBO reports AOP Published online: 11 April 2003Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapieAchim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique KrÒ¼ger & MichaelBeekes Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin, GermanyReceived 13 February 2003; Accepted 13 March 2003; Published online 11April 2003.Abstract :Scrapie, bovine spongiform encephalopathy and chronic wasting diseaseare orally communicable, transmissible spongiform encephalopathies(TSEs). As zoonotic transmissions of TSE agents may pose a risk to humanhealth, the identification of reservoirs for infectivity in animaltissues and their exclusion from human consumption has become a matterof great importance for consumer protection. In this study, a variety ofmuscles from hamsters that were orally challenged with scrapie wasscreened for the presence of a molecular marker for TSE infection, PrPSc(the pathological isoform of the prion protein PrP). Sensitive westernblotting revealed consistent PrPSc accumulation in skeletal muscles fromforelimb and hindlimb, head, back and shoulder, and in tongue.Previously, our animal model has provided substantial baselineinformation about the peripheral routing of infection in naturallyoccurring and orally acquired ruminant TSEs. Therefore, the findingsdescribed here highlight further the necessity to investigate thoroughlywhether muscles of TSE-infected sheep, cattle, elk and deer containinfectious agents. http://www.emboreports.org/ some previous data on TSE in muscle; J69CVO BSE 1 5SCRAPIE AGENT IN MUSCLE - PATTISON I A (1990) VETERINARY RECORD, 20JANUARY 1990, p.68Background1 Dr Pattison, a retired but eminent worker on scrapie for many years inthe AFRC, has pointed out that in one of his experimental studies ofscrapie in goats he found scrapie agent in the biceps femoris (rump)muscle of one animal with clinical disease but not in 2 others withclinical disease and in none with pre-clinical disease. MAFF have basedtheir policy on BSE in regard to meat (beef) on the results of studiesof natural scrapie (ie disease occurring under farm conditions) in bothsheep and goats by Hadlow 1979, 80, 81.Other Infectivity Studies2. These studies on 52 animals by equally eminent scrapie workers(Hadlow et al) revealed no evidence whatever of infectivity in skeletalmuscle from these natural cases either in the pre-clinical or evenclinical stages of disease.It is clear that the pathogenesis of experimental (Pattison) and natural(Hadlow) scrapie may be different and it was therefore considered wiseto base present policy on knowledge of the natural disease.3. Pattison exposed his 14 goats to intracerebral inoculation of thricepassaged scrapie virus (in goats). This may have resulted in strainselection and/or mutation of the natural agent. In contrast Hadlow'sstudy involved natural strains (probably multiple) in a flock with ahigh incidence of disease in which exposure would almost certainly havebeen by the mouth.4. The fact that Hadlow identified no infectivity in muscle by mouseinoculation (whereas some other tissues not normally consumed haddetectable infectivifcy) shows that cross contamination of his tissuesdid not occur. Pattison's experiments were reported about 20 yearsearlier when much less was known about Scrapie. In the interveningperiod the knowledge available to Hadlow on the insensitivity of scrapieagent to heat became available. There is therefore at least thepossibility that Pattison's instruments were not sterilised effectively,thus possibly giving the false positive result for muscle.5. Pattison used a more sensitive model for the detection ofinfectivifcy, namely goats, whereas Hadlow used mice ie necessitatingcrossing the species barrier and possibly reducing the test sensitivity.90/1.19/9.1CVO BSE 1 56. In regard to the choice of species for agent assay, mice (Hadlow),these would be guaranteed free of pre-existing Scrapie infection.Pattison could offer no such guarantee that this was the case in theanimal to which muscle was passaged and disease could have developedfrom exposure from a source other than muscle.7. Pattison did not report that his recipient animals, including the oneinoculated with muscle, were examined by histopathology to confirm thepresence of disease. This is a significant deficit. Clinical diagnosisalone is not acceptable as adequate evidence for the existence of scrapie.8. Even in Pattison's studies only in 1 out of 14 goats was infectivitydetected in muscle and that was in a CLINICAL case. In BSE all clinicalcases are notified and do not enter any food chain.9. The last paragraph of Pattison's letter is illogical. Furthermore,this is no evidence whatsoever that scrapie or BSE is a danger to man.W A WATSON 19 January 1990Private Offices Mr K C Meldrum Mrs E Attridge Mr R Lowson Ms L Austin MrR Bradley 90/1.19/9.2 http://www.bseinquiry.gov.uk/files/yb/1990/01/19009001.pdf
CONSIDER the fact non-documented TSEs have been circulating in the US bovine for decades.CWD in deer and elk for decades and spreading.Scrapie in sheep and goats for decades and spreading.TME in the USA as well.ALL rendered for human/animal consumption for decades in the USA(don't think too much mink have been rendered due to musk gland?)THE lack of TSE surveillance in both animals and MAN.4.5 MILLION ALZHIEMER'S a year with a projected 20 million by 2050.4 studies showing from 3 to 33 percent of those diagnosed with Alzheimer'safter autopsy, actually had CJD (Yale, Duke, PA and a Mexican study).one-in-a-million?amplfication via medical/surgical arena?NOW, the important question would be, how many of those new atypical TSE showing up in cattle and sheepthat are very similar to sporadic CJD, how those tissues, blood and blood products infectivity studies might comeout and IF BSE propagates as both nvCJD and sporadic CJDs, then the blood ban is not complete. either way,the public looses. FOR this reason the damn BSE/nvCJD only theory is more dangerous than the agent itself.YOUR missing 85%+ of all cases, and the agent (however many different phenotypes there maybe)continues to spread and expose. NOW, for a final thought; -------- Original Message --------Subject: TSE REPORT USA September 14, 2004Date: Tue, 14 Sep 2004 14:54:52 -0500From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: [email protected] by National Center for Animal Health Programs Eradication and Surveillance Team July 31, 2004 SCRAPIE INFECTED AND SOURCE FLOCKS AS of July 31, 2004, there were 71 scrapie infected and source flocks (figure 3). There were 4 new infected and source flocks reported in July (figure 4) with a total of 90 flocks reported for FY 2004 (figure 5). The total infected and source flocks that have been released in FY 2004 are 62 (figure 6), with 15 flocks released in July. The ratio of infected and source flocks released to newly infected and source flocks for FY 2004 = 0.69 : 1. IN ADDITION, AS OF JULY 31, 2004, 282 SCRAPIE CASES HAVE BEEN CONFIRMED and reported by the National Veterinary Services Laboratories (NVSL) in FY 2004, OF WHICH 42 WERE RSSS CASES (figure 7). This includes 60 NEWLY CONFIRMED CASES IN JULY 2004 (figure 8). THIRTEEN cases of scrapie in GOATS have been reported since 1990 (figure 9). ONE NEW GOAT CASE WAS REPORTED IN FY 2004. New infected flocks, source flocks, and flocks released or put on clean-up plans for FY 2004 are depicted in figure 10... snip... http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html Emergency Programs * Imported Belgium/Netherlands Sheep Test Results APRIL 2002 snip... The Western-blot test however cannot differentiate between scrapie and BSE. The only known validated method to differentiate between these two diseases requires a series of mouse bioassay systems, which take at least 23 years for completion. snip... http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fs_ahvtsheeptr.pdf -------- Original Message -------- Subject: Re: AW: [BSE-L] USDA did not test possible mad cows - Dr. Detwiler, what about those sheep? Date: Sun, 13 Jun 2004 11:27:24 -0500 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy Greetings list members, Thought I should let the list know that Dr. Detwiler kindly replied to my question about the delayed 'atypical' TSE testing in the Vermont sheep and tried to explain what caused the delay. If I interpreted it correctly, seems it was the fault of the U.K. ; -------- Original Message -------- Subject: Sheep Date: Sat, 12 Jun 2004 14:26:04 EDT From: [email protected] To: [email protected] Mr. Singeltary. I hope this finds you well. As you are aware I left the USDA last year. I can only update you on the sheep before that time. Contact was established with the UK on doing the bioassay studies. They agreed. However, we were prioritized after their own needs, hence the delay. I am aware that there are now additional labs in Europe running the mouse bioassay strain typing. You will have to contact USDA for further word. Linda Detwiler ========= My reply to Dr. Detwiler; -------- Original Message -------- Subject: Re: Sheep Date: Sat, 12 Jun 2004 13:53:57 -0500 From: "Terry S. Singeltary Sr." To: [email protected] References: <[email protected]> hello Dr. Detwiler, thanks for your kind reply. > However, we were prioritized after their own needs, hence the delay. not sure i understand that? > You will have to contact USDA for further word. already done that, and there answer was; >5/20/04 > >Dear Mr. Singeltary, > >The Western blot tests on these animals were completed in April of this >year. That means that we can begin the mouse inoculations. To get the >results of the Western blot tests, you will need to submit a Freedom of >Information Act request through our FOIA office. The FAX number there is >301-734-5941. > >Have a nice day, > >Jim Rogers >APHIS LPA > and with my previous attempts for information via the FOIA through this administration (as you are probably very well aware of) they have
 

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